Trypanosoma brucei rhodesiense and T. brucei gambiense, the causative agents of
Human African Trypanosomiasis, are transmitted by tsetse flies. Within the vector,
the parasite undergoes through transformations that prepares it to infect the human
host. Sequentially these developmental stages are the replicative procyclic (in which the
parasite surface is covered by procyclins) and trypo-epimastigote forms, as well as the
non-replicative, infective, metacyclic form that develops in the vector salivary glands.
As a pre-adaptation to their life in humans, metacyclic parasites begin to express and
be densely covered by the Variant Surface Glycoprotein (VSG). Once the metacyclic
form invades the human host the parasite develops into the bloodstream form. Herein
the VSG triggers a humoral immune response. To avoid this humoral response, and
essential for survival while in the bloodstream, the parasite changes its cover periodically
and sheds into the surroundings the expressed VSG, thus evading the consequences
of the immune system activation. Additionally, tools comparable to quorum sensing are
used by the parasite for the successful parasite transmission from human to insect. On
the other hand, the human host promotes clearance of the parasite triggering innate
and adaptive immune responses and stimulating cytokine and chemokine secretion. All
in all, the host–parasite interaction is extremely active and leads to responses that need
multiple control sites to develop appropriately.